Синдром Малуфа: описание, генетика и диагностика

Malouf syndrome (also known as "congestive cardiomyopathy hypergonadotropic hypogonadism syndrome") is a congenital disorder that causes one or more of the following symptoms: mental retardation, ovarian dysgenesis, congestive cardiomyopathy, broad nasal base, blepharoptosis, and bone abnormalities, and occasionally marfanoid habitus (tall stature with long and thin limbs, little subcutaneous fat, arachnodactyly, joint hyperextension, narrow face, small chin, large testes, and hypotonia). This disease is named after J. Malouf, who performed a case study on a family with this disease in 1985. The study consisted of two sisters displaying the above symptoms. The parents of the sisters were first degree cousins, suggesting the possibility of a genetic disorder. In 1992, a new case study of an 18 year old female conducted by Narahara et al. resulted in similar findings as Malouf. Although the prevalence of Malouf syndrome is unknown, there are less than 20 affected families discussed in literature. While there is no specific cure for Malouf syndrome, symptoms can be treated. The treatment options individualized and should be determined by a doctor or specialist.

Malouf syndrome involves an autosomal dominant inheritance pattern. It is caused by a heterozygous missense mutation in the LMNA gene located on chromosome 1 (1q22). The lamin family of proteins are components of the nuclear lamina that consists of a protein network within the inner nuclear membrane that determine nuclear stability, chromatin structure and gene expression. Mutations in this gene can lead to several diseases besides Malouf syndrome, such as familial partial lipodystrophy, limb girdle muscular dystrophy, Hutchinson Gilford progeria syndrome etc.

There is no set criteria used to diagnose Malouf syndrome. Signs and symptoms such as congestive or dilated cardiomyopathy, ovarian dysgenesis in females or primary testicular failure in males, mental retardation, broad nasal base, blepharoptosis, skin lesions, and skeletal abnormalities are used as a reference to diagnosis this rare disease, and genetic testing of the LMNA gene can serve as a way to confirm any diagnosis made. Malouf syndrome was first diagnosed in 1985 by Dr. Joe Malouf. Dr. Malouf examined two sisters who exhibited congestive cardiomyopathy associated with ovarian dysgenesis, secondary hypergonadotropic hypogonadism, bilateral ptosis, and prominent nasal bones. Dr. Malouf noted that this disease may be familial as the two sisters were children of first degree cousins. In 1992, Kouji Narahara examined an 18 year old girl who displayed the same symptoms seen by Dr. Malouf. In order to treat dilated cardiomyopathy, doctors normally use a combination of drugs. Depending on your symptoms, you might need two or more drugs. The following is a list of drugs that are used to treat dilated cardiomyopathy. Drugs: Dilated cardiomyopathy was originally classified as a rare disease, but the possibility of a familiar substrate was ignored. Dilated cardiomyopathy was later found to be a major cause of heart failure, especially among young patients. Dilated cardiomyopathy began to be identified as a systemic condition rather than an isolated disease. Even despite these major efforts and contributions, the incidence and prevalence of dilated cardiomyopathy remain unknown.